The field of regenerative medicine generally aims to replace damaged and diseased tissues with functional equivalents that will integrate with the host tissue and restore normal function over time. The general approach for engineering tissue constructs is to coordinately combine relevant cell types with biophysical/chemical cues on an appropriate scaffolding material. The scaffolding material for building tissue equivalents plays a significant role in modulating cell behavior and resulting tissue function. To achieve desired tissue function, efforts are taken to optimize scaffold properties such as surface chemistry, porosity, pore morphology, substrate stiffness, and biodegradation rate (Carletti, 2011; Mikos, 2006). In order to systematically design critically-sized, three-dimensional (3D) scaffolds that can serve as complex tissue equivalents it is important to be able to independently tune these properties.
One of the primary obstacles in building critically-sized engineered tissue constructs includes the diffusion limit of oxygen and nutrients. Scaffold constructs that exceed dimensions beyond several hundred micrometers are generally prone to necrosis at the core of the construct and ultimately fail to integrate with host tissue in the long-term due to lack of blood perfusion (Lokmic and Mitchell, 2008; Rouwkema et al., 2008). The natural steps of vascularization within a critically-sized construct do not generally occur within a sufficient time frame to supply the entire construct with necessary oxygen and nutrients. Furthermore, such necrosis can stimulate inflammatory responses in vivo, leading to undesirable outcomes with the implantation of the constructs. Therefore, there is a need in the art for an improved scaffold construct, e.g., for critically-sized tissue engineering applications.